Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center

A leaky gut may be the root of some cancers forming in the rest of the body, a new study published online Feb. 21 in PLoS ONE by Thomas Jefferson University researchers suggests.

It appears that the hormone receptor guanylyl cyclase C (GC-C)—a previously identified tumor suppressor that exists in the intestinal tract—plays a key role in strengthening the body’s intestinal barrier, which helps separate the gut world from the rest of the body, and possibly keeps cancer at bay. Without the receptor, that barrier weakens.

A team led by Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center, discovered in a pre-clinical study that silencing GC-C in mice compromised the integrity of the intestinal barrier. It allowed inflammation to occur and cancer-causing agents to seep out into the body, damaging DNA and forming cancer outside the intestine, including in the liver, lung and lymph nodes.

A weakened intestinal barrier has been linked to many diseases, like inflammatory bowel disease, asthma and food allergies, but this study provides fresh evidence that GC-C plays a role in the integrity of the intestine. Strengthening it, the team says, could potentially protect people against inflammation and cancer in the rest of the body.

“If the intestinal barrier breaks down, it becomes a portal for stuff in the outside world to leak into the inside world,” said Dr. Waldman. “When these worlds collide, it can cause many diseases, like inflammation and cancer.”

The role of GC-C outside the gut has remained largely elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. They’ve used to it better predict cancer risk, and have even shown a possible correlation with obesity.

Reporting in the Journal of Clinical Investigation, Dr. Waldman colleagues found that silencing GC-C affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

However, its role in intestinal barrier integrity, inflammation, and cancer outside the intestine is new territory in the field.

A new drug containing GC-C is now on the verge of hitting the market, but its intended prescribed purpose is to treat constipation.

This study helps lays the groundwork, Dr. Waldman said, for future pre-clinical and clinical studies investigating GC-C’s abilities beyond those treatments in humans, including prevention and treatment of inflammatory bowel disease and cancer.

“We’ve shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer. And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier,” Dr. Waldman said. “Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier.”

Despite the decline in cancer incidence and mortality rates in the United States, disparities in cancer burdens continue to exist among certain population groups and the gap continues to widen. The Philadelphia region in particular has a disproportionately high number of residents suffering from cancers, many of which are preventable and treatable.

Such disparities include differences in incidence, prevalence, mortality and burden of cancer and related adverse health conditions. Disparate population groups may be characterized by gender, age, race and ethnicity, income, social class, disability, geographic location or sexual orientation.

“I have dedicated my career to the treatment of cancer patients and have had the opportunity to experience, as a physician and as a researcher, the significance cancer disparities can have on the outcome of a patient’s treatment,” said Dr. Mitchell. “The first step in the elimination of these disparities is to raise awareness through public and professional education about what resources are available to groups in their fight against cancer.”

The Center aims to accomplish its mission through the facilitation of disparities-focused research, researcher and clinician education, training and teaching, and increased patient access to quality supportive services, such as palliative care, cancer screening and prevention, and survivorship programs.

Dr. Mitchell and her fellow clinicians and researchers at Jefferson are dedicated to the ongoing study of cancer and other health disparities among patients of diverse ethnic and socioeconomic backgrounds. They have created strategic priorities for eliminating such disparities through innovative research, education and training, advocacy, community outreach, and quality medical care.

The need for research into cancer, and other health care disparities, has become increasingly evident in recent years as doctors and scientists learn more about how slight variations in genetic makeup can have drastic effects on the way cancer invades an individual’s body. Knowing that these disparities exist can improve how screening processes are established and help doctors understand which treatments will and will not be effective.

Dr. Mitchell has spent her medical career helping individuals in medically underserved areas to realize that simple changes in lifestyle can have a dramatic impact on cancer care. Through her work, Dr. Mitchell has demonstrated the importance of community service and outreach especially to those individuals who may not have the means to seek out more conventional medical advice.

She holds board certifications in both Internal Medicine and Medical Oncology and is a Fellow in the American College of Physicians. She has also served as the Program Leader in gastrointestinal oncology for more than 15 years and has a focused research effort in aggressive breast cancers.

“We want all researchers and clinicians to be aware of the disparities that exist in cancer diagnoses among diverse ethnic groups so that they can incorporate these important factors into their research efforts and clinical practice,” said Dr. Mitchell.

“The Center will also provide patients with contact information for cancer advocacy and support groups both locally and nationally that serve the needs of their demographic background. We are proud to host and sponsor several annual events where patients can come together to share their stories and plan for a future free of cancer disparities,” she said.

The PBCC’s grants are made possible through contributions from state taxpayers who choose to contribute all or part of their state income tax refund to the program.

Dr. Tanaka’s research focuses on breast cancer metastasis. When cancer metastasizes, cancer cells enter the distal organs through the blood vessels. Dr. Tanaka envisions those vessels as a gateway for the cells and wants to close it as tight as possible to prevent the cancer from spreading further.

Her team developed a new drug called ESTA to block the entry of breast cancer cells into the tissue. Early data show that mice treated with the drug had 60 percent less metastases without toxicity.

From the left: Ashiwel Undieh, Chair of Pharmaceutical Sciences, Pat Halpin-Murphy, founder of PBCC, Dr. Tanaka, and Rebecca Finley, Dean of the Jefferson School of Pharmacy

“I would like to express my sincere gratitude to the tax payers for their generous support for my breast cancer research to help eradicate this deadly disease,” Dr. Tanaka said. “We believe that success with our strategy may transform current breast cancer therapy and move us one step closer to a cure.”

Dr. Tanaka is one of three researchers who received funding through PBCC’s Breast and Cervical Cancer Research initiative. The other recipients are from the University of Pennsylvania and Penn State Hershey Cancer Institute.

“We’re extremely proud of Dr. Tanaka’s recognition by the Pa. Breast Cancer Coalition and thankful for the people in Pennsylvania who donated to help support these grants, as well as the PBCC for their efforts to raise awareness about breast cancer,” said Rebecca Finley, PharmD, M.S., Dean of Jefferson’s School of Pharmacy. “Dr. Tanaka’s work with this promising new drug will only help us better understand and potentially better treat this important health issue in women.”

The PBCC kicked off its annual Refunds for Breast and Cervical Cancer Research campaign to fund the cancer researchers on Monday, Feb. 13 at City Hall with Councilmen Dennis O’Brien.

Since 1997, more than $2.8 million has been donated to the Refunds for Research campaign and 71 grants have been awarded to Pennsylvania researchers looking for the cause of and cure for these common cancers in women.

Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson’s Kimmel Cancer Center suggests.

Reporting in a recent issue of Cancer Research, Karen Knudsen, Ph.D., a Professor of Cancer Biology, Urology and Radiation Oncology at Thomas Jefferson University, Supriya Shah, a Jefferson graduate student in Cancer Biology, and colleagues observed in a pre-clinical study that curcumin suppresses two known nuclear receptor activators, p300 and CBP (or CREB1-binding protein), which have been shown to work against ADT.

ADT aims to inhibit the androgen receptor—an important male hormone in the development and progression of prostate cancer—in patients. But a major mechanism of therapeutic failure and progression to advanced disease is inappropriate reactivation of this receptor. Sophisticated tumor cells, with the help of p300 and CBP, sometimes bypass the therapy.

Thus, development of novel targets that act in concert with the therapy would be of benefit to patients with castration-resistant prostate cancer.

For the study, prostate cancer cells were subjected to hormone deprivation in the presence and absence of curcumin with “physiologically attainable’ doses. (Previous studies, which found similar results, included doses that were not realistic.)

Curcumin augments the results of ADT, and reduced cell number compared to ADT alone, the researchers found. Moreover, the spice was found to be a potent inhibitor of both cell cycle and survival in prostate cancer cells.

To help support their findings, the researchers also investigated curcumin in mice, which were castrated to mimic ADT. They were randomized into two cohorts: curcumin and control. Tumor growth and mass were significantly reduced in the mice with curcumin, the researchers report.

These data demonstrate for the first time that curcumin not only hampers the transition of ADT-sensitive disease to castration-resistance, but is also effective in blocking the growth of established castrate-resistant prostate tumors.

“This study sets the stage for further development of curcumin as a novel agent to target androgen receptor signaling,” said Dr. Knudsen. “It also has implications beyond prostate cancer since p300 and CBP are important in other malignancies, like breast cancer. In tumors where these play an important function, curcumin may prove to be a promising therapeutic agent.”

On Tuesday, November, 17th 2011, the Kimmel Cancer Center at Jefferson held the Third Annual Men’s Event benefiting prostate cancer research and patient care at the Prime Rib Restaurant in Philadelphia. The Men’s Event was emceed by Philadelphia Eagles Longsnapper, motivational speaker and magician, Jon Dorenbos.

Receiving the Symbol of Courage was John Beuhler, prostate cancer survivor and grateful patient of Thomas Jefferson University Hospital. The Symbol of Caring was presented to Kenneth Boone, board member of Thomas Jefferson University Hospital.

Special guests included Amber-Joi Watkins, Miss USA Pennsylvania and Julianna White, Miss USA New Jersey. Guests enjoyed a dinner, silent and live auction, and casino.

The Lead Sponsor was Bill Frankel of Frankel Enterprises. Kimmel Cancer Center would also like to thank the following sponsors:

Sponsor Company / Group

Silent Auction/ Company

AP Executive Management

Algar Ferrari of Philadelphia

Barry Bressler, Esq. and Betty Gross Eisenberg

American Male Salon

BlankRome

Annie-Prue

Boone Properties, LLC

Atlantic City Country Club

Chamber Orchestra of Philadelphia

Bistrot La Minette

Charles Pike Construction

Blackfish Restaurant

Citi

Blue Horizons Dive Center

Commonwealth Agency, Inc.

Boyds

Dann, Dorfman, Herrell & Skillman, PC

Chadds Ford

David Yurman Jewelers

Chelsea Hotel

DBA The Wyndon Group

City of Philadelphia Mural Arts Program

Deitz & Watson

Cooperage Wine and Whiskey Bar

Department of Medical Oncology

Cross Winds Flight School

Dilworth Paxson

D’Angelo’s Restaurant

Drs. Gomella and Family

David Yurman

Electronic Ink

Dock’s Oyster House/Knife & Fork Atlantic City

Firstrust

Drexel University Men’s Basketball

Frankel Enterprises

Electronic Ink

Heffler, Radetich & Saitta

Fencing Academy of Philadelphia

Hi Fi House

Fogo de Chao

Koegle Family

Four Seasons Hotel

M&T Bank

Kenneth Freeling and Sue Cimbricz

McCullough Models

From My Harp – Cheryl Kripke Cohen

PREIT

Gomella Family

Rodin IFC

Henry A. Davidsen

Stradley Ronon

Hidden Creek Golf Club

TD Bank

Holt’s Cigar Company

Unique Products

Hortman Aviation Services

US Bank

J. Lohr

Jacques Ferber

Joseph Anthony Spa

Jump NEA

Kramer Portraits New York

La Prairie

Lacoste

Lacroix

Le Castagne

Lehigh Valley

Limoncello

Lord & Taylor, Bala Cywyd

Lucky Strikes

Manito Equestrian Center

May’s Landing Golf Club

McCullough’s Emerald Golf Links

Merion Country Club

Mid-Atlantic Restaurant

Milkboy

Monsu

Nangellini

Nicole Miller

Pennsylvania Paragliding

Philadelphia Sports Club

Piper Memorial Airport

Quaker State Light Sport Flight Academy, LLC.

Ralph Lauren

Ristorante Panorama

Saks Fifth Avenue, Bala Cynwyd

Salon Ziza

Segway Tours

Skirmish

St. Joe’s University Men’s Basketball

Target Masters Gold Membership

The Chamber Orchestra of Philadelphia

The Little Tuna

The Prime Rib

The Union Trust

The Vesper Club

Thomas J Duffy, Esq.

Tiffany’s

Time Restaurant

Twin Pines Stables and Unique Industries

Twisted Tail

Ultimate Shave

Union League of Philadelphia

Villanova University Men’s Basketball

Villanova University Football

Victory Brewing Co.

Vintage Wine Bar

West Avenue Grille

Whitewater Challengers

The Third Annual Men’s Event would not have been possible without the tremendous work and support of our Committee members:

Barry Bressler

Rose Cunningham

Robert DeBolt

Marc Feller

Marc Franzoni

Peter Gistelinck

Bruce Goldman

Tricia Gomella

Niels Haun

Mark Juliano

Erik Knudsen

Bryan Koegel

John LeVine

Bill McCullough

Meredith Seigle

Roger Vander Klock

Thomas Walls

Special thanks to Gerard Tomko Wedding Photography for donating his services in-kind.

Previously, Mr. Khariton had been the Administrative Director for the Department of Radiation Oncology at Cooper University Hospital in Camden, N.J., for the past eight years.

“I”m looking forward to working for an NCI-designated cancer center that provides excellent clinical car, partakes in innovative research, and has a well-respected medical school,” says Alex.

Alex is also Co-Chair of the Reimbursement and Economic committee for the SROA (Society of Radiation Oncology Administrators) and a member of the American Society for Therapeutic Radiology and Oncology (ASTRO).

The new hire announcement was featured online in the Philadelphia Business Journal’s “People on the Move” section:

The researchers used various in vitro and in vivo model systems to show that elevated levels of cyclin D1 promotes CIN and correlate with CIN in the luminal B breast cancer subtype. Cyclin D1 protein is elevated in breast, prostate, lung and gastrointestinal malignancies.

The findings suggest that shifting towards drugs targeting CIN may improve outcomes for patients diagnosed with luminal B subtype. Luminal B breast cancer has high proliferation rates and is considered a high grade malignancy.

Estrogen or progesterone receptor positive and HER2 positive cancers indicate luminal B, and about 10 percent of patients are diagnosed with it every year, though many do not respond well to treatment. The identification of CIN in luminal B provides a new therapeutic opportunity for these patients.

“Cyclin D1 has a well defined role in cell proliferation through promoting DNA replication,” says Dr. Pestell. “My team was the first to discover that cyclin D1 also has alternate functions, which include regulating gene transcription at the level of DNA. We were interested in discovering the function of DNA associated cyclin D1.”

To help answer this, the researchers, including lead author Mathew C. Casimiro, Ph.D., of the Department of Cancer Biology at Thomas Jefferson University, first needed to directly access cyclin D1′s role in gene regulation.

They applied an analysis known as ChIP sequencing to study the protein’s interactions with genes that comprise the entire mouse genome, and found it occupied the regulatory region of genes governing chromosomal stability with high incidence.

They went on to show cyclin D1 promoted aneuploidy and chromosomal rearrangements typically found in cancers.

Faulty chromosomes—either too many or too few, or even ones that are the wrong shape or size—have been shown to be the crux of many cancers. However, a major question of cancer genetics is the mechanisms of CIN. What causes the breakdown in chromosomal stability?

As cyclin D1 expression is increased in the early phases of tumorigenesis, cyclin D1 may be an important inducer of CIN in tumors.

To analyze the association between CIN and cyclin D1 expression in the context of breast cancer, the team aligned an expression of a 70-gene set with the highest CIN score against over 2,000 breast cancer samples. They stratified the samples based on previously described subtypes and aligned them with cyclin D1 expression profiled across the dataset.

A significant correlation among CIN, cyclin D1 and the luminal B subtype was identified, and it was apparent that the relationship between these levels was subtype specific.

“Interestingly, previous studies have presented contradictory results,” Dr. Pestell says. “Many studies have suggested a positive correlation between cyclin D1 expression and outcomes, while others have shown reduced survival. Here, we’ve dug deep, using a genome-wide analysis, and found that overexpression of the protein appears to be directly associated with the genes involved in CIN and this correlates with the luminal B subtype.”

Drugs targeting chromosomal instability for cancer therapy have been explored, but a sub-stratification rationale for the luminal B subtype has not been established. The research presented in this study suggests such a target is worthy of further investigation.

“There is a big drive towards using targeting therapies for stratified breast cancers,” says Dr. Casimiro. “What we are thinking is that there are a growing number of drugs that target aneuploidy, like AICAR and 17-AAG, that may be used as an adjuvant therapy in patients with luminal B breast cancer.”

Juan P. Palazzo, M.D., an anatomic/surgical pathologist at Thomas Jefferson University Hospital and the Jefferson Breast Care Center, has authored a book that tackles the hard cases in breast disease pathology faced by many clinicians in the healthcare world today.

According to Amazon, Difficult Diagnoses in Breast Pathology (Demos Medical) provides a highly visual presentation of the major problems and questions that a pathologist is likely to encounter in the evaluation of common and uncommon breast diseases.

Addressing real-world diagnostic problems faced in daily practice, the book includes needle core biopsy interpretation, diagnosis of precursor lesions, early stage disease, and recognition of neoplastic mimics and other misleading variants.

Each chapter is authored by a recognized expert in the area, and includes hundreds of high-quality images.

“This is a welcome new addition to this field and it delivers with concise, clear writing, ample illustrations, and appropriate comments on ancillary techniques. This latest addition to the field of histomorphology of (surgical) breast disease compares favorably with many more extensive books,” writes Doody’s Reviews.

Dr. Palazzo is pathologist with over 25 years experience and has been named a U.S. News & World Report “Top Doctor.”

Xinglei Shen, M.D., a resident in Jefferson’s Department of Radiation Oncology and a part-time master’s degree student in the Jefferson School of Population Health

Brachytherapy for high-risk prostate cancers patients has historically been considered a less effective modality, but a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests otherwise. A population-based analysis looking at almost 13,000 cases revealed that men who received brachytherapy alone or in combination with external beam radiation therapy (EBRT) had significantly reduced mortality rates.

Their findings are reported online January 23 in the International Journal of Radiation Oncology,Biology,Physics.

Brachytherapy involves the precise placement of radiation sources directly at the site of a tumor and is typically used to treat low and intermediate risk prostate cancers. However, brachytherapy treatment for high-risk patients is less common and controversial, given in part to early retrospective studies that found it to be associated with lower cure rates compared to EBRT.

Many experts believe that these early series were limited by poor brachytherapy technique, and that high-quality contemporary brachytherapy may be an effective tool against high-risk prostate cancer.

“The study contradicts traditional policies of using brachytherapy in just low and intermediate risk patients by suggesting there may instead be an improvement in prostate cancer survival for high-risk patients,” said co-author Timothy Showalter, M.D., assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital, and associate research member of Jefferson’s Kimmel Cancer Center. “Although studies like this cannot prove an advantage for brachytherapy, our report does suggest that brachytherapy is no less effective than EBRT and should be considered for some men with high-risk prostate cancer.”

Researchers identified 12,745 Surveillance, Epidemiology and End Results database patients diagnosed from 1988 to 2002 with high-grade prostate cancer of poorly differentiated grade and treated with brachytherapy (7.1 percent), EBRT alone (73.5 percent) or brachytherapy plus EBRT (19.1 percent). The team used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on prostate cancer-specific mortality.

Treatment with brachytherapy alone or brachytherapy in combination with EBRT, the researchers found, was associated with significant reduction in prostate cancer-specific mortality rates compared to EBRT alone.

Significant predictors of use of brachytherapy or brachytherapy plus EBRT were younger age, later year of diagnosis, urban residence and earlier T-stage.

According to the researchers, including lead author Xinglei Shen, M.D., a resident in Jefferson’s Department of Radiation Oncology and a part-time master’s degree student in the Jefferson School of Population Health, the study’s findings provide ample evidence to further study brachytherapy as part of an effective treatment strategy for men with high-grade prostate cancer.

“Today, for the most part, brachytherapy is not being used for these high-risk patients or even recommended,” Dr. Shen said. “But if you look at the biology and theory behind it, it makes sense: you can really give a lot more dose with brachytherapy than with EBRT alone to the prostate. And this presents an opportunity for high-risk patients.”

CURE OM has announced the inaugural Eyes on a Cure: Patient and Caregiver Symposium to be held on June 16th and 17th, 2012. The meeting will be held one month after the first CURE OM Scientific Meeting (for physicians and researchers) with the goal of bringing the latest news from the ocular melanoma scientific community directly to patients and their loved ones. Eyes on a Cure will bring patients, caregivers and researchers from around the world together to offer educational sessions, support groups led by oncology social workers, sessions on complementary therapies, as well as informal time for networking.

This first patient and caregiver symposium will be held in Philadelphia at the Kimmel Cancer Center of Thomas Jefferson University. Confirmed speakers include: Carol Shields, Takami Sato, David Eschelman, Carin Gonsalves, and James Pingpank.

The study published in the open access online journal PLoS ONE tested the use of intravenous ascorbic acid (vitamin C) three times a week over an eight week cycle in nine patients with metastatic stage IV pancreatic cancer in addition to standard gemcitabine and erlotinib chemotherapy regimens.

“These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients,” wrote the team of researchers from the Kimmel Cancer Center at Jefferson as well as the National Institutes of Health (NIH). “This combination with the observed response to treatment suggests the need for a phase II study of longer duration.”

Daniel A. Monti, MD, Executive and Medical Director of the Jefferson-Myrna Brind Center of Integrative Medicine and lead author of the study said, “We are pleased and encouraged by these results.”

Dr. Monti added, “it is a Jefferson priority to study promising therapies for pancreatic cancer. It is crucial to explore anything that might feasibly give these patients an edge. We are now actively enrolling eligible patients into the Phase II trial.”

Jefferson’s Kimmel Cancer Center has started a Phase I clinical trial investigating the latest prostate cancer chemotherapy drug to extend survival, Cabazitaxel, in combination with radiation and hormone therapy. This first-of-its-kind multimodality approach could improve disease control and eventually survival for locally advanced prostate cancer patients.

Cabazitaxel was approved in the U.S. for second-line use in advanced hormone-refractory prostate cancer in men in 2010, and has been described as a major advance in chemotherapy for advanced prostate cancer. It extended overall survival by 2.4 months when compared with mitoxantrone in patients who were previously treated with docetaxel. However, a multimodality approach with the drug has never been studied.

“We know the drug is effective in prostate cancer, but there is no study with radiation and hormone therapy yet,” said principal investigator Jianqing Lin, M.D., an assistant professor of medical oncology at Thomas Jefferson University Hospital. “Concurrent radiation may have a better control for localized disease, and better long-term survival for these high-risk patients.”

IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor; androgen deprivation therapy is a treatment to suppress or block the production or action of male hormones. Enrolled men will receive weekly treatments of the chemotherapy drug and hormone therapy and then every three months until two years after completion of IMRT.

In an interview with KYW Newsradio, Dr. Andrews explains that the first step of the trial will be a surgical procedure to take cells from the brain tumor. He adds, ”We then take the tumor cells and treat them with a drug that will induce cell death. The drug itself actually interacts with the immune system.”

Afterwards, the cells are placed in the stomach to work with the immune system to attack the malignant tumor.

Each year, approximately 70,000 Americans are diagnosed with bladder cancer. In the past, detecting tumors on the bladder wall has been a challenge but a new procedure at Jefferson, blue light cystoscopy, allows doctors to better see where the tumors are located.

In a Dec. 1 news article published in the American Association for Cancer Research journal Cancer Discovery, Marja Nevalainen, M.D., Ph.D., an associate professor of cancer biology, medical oncology, and urology, offers up her insight for a story focusing on the challenges and opportunities postdocs face in an increasingly tight job market.

KCC's Dr. Marja Nevalainen

“Typically, postdoctoral training is overseen by one mentor,” says Nevalainen, who also oversees junior faculty and graduate education at the KCC. Nevalainen suggests an advisory committee of 2 or 3

members for each postdoctoral trainee, especially if the postdoc is supported by an institutional training grant (T32).

In addition, “If you have a strong basic scientist as one mentor, input from a physician–scientist may facilitate thinking about research designs in the lab that have translational applications such as therapy and biomarker development.”

As part of the Section on Medical Sciences, Dr. Pestell was elected as an AAAS Fellow for his distinguished contributions to cancer care as director of two National Cancer Institute cancer centers, including the KCC and Lombardi Cancer Center at the Georgetown University Medical Center, and research identifying new molecular targets (cyclins, acetylation) and light activated gene therapy.

Election as a AAAS Fellow is an honor bestowed upon AAAS members by their peers.

Dr. Pestell, who was named Director of the KCC in November 2005, is a highly respected researcher and clinician whose current work is focused on developing new cancer therapies that specifically target tumors, and reduce the side effects that are associated with commonly used cancer treatments such as chemotherapy and radiation.

He has made significant contributions to our understanding of cell cycle regulation and the disturbances that can lead to the malignant transformation of cells. Dr. Pestell has particular expertise in hormonally-responsive tumors, such as those of the breast and prostate, and his work is directed toward the eventual discovery of novel therapies for these cancers.

This year 539 members have been awarded this honor by AAAS because of their scientifically or socially distinguished efforts to advance science or its applications. New Fellows will be presented with an official certificate and a gold and blue (representing science and engineering, respectively) rosette pin on Saturday, February 18 at the AAAS Fellows Forum during the 2012 AAAS Annual Meeting in Vancouver, B.C., Canada.

This year’s AAAS Fellows will be formally announced in the AAAS News & Notes section of the journal Science on Dec. 23.

Also, as part of the Section on Medical Sciences, Hideko Kaji, Ph.D., of the Department of Biochemistry and Molecular Biology of Thomas Jefferson University, was named a AAAS fellow for her distinguished contributions to biology by discovering specific tRNA binding to mRNA-ribosome complexes, N-terminal protein modification by arginine, and ribosome recycling, the last step of protein synthesis.

Fellows elected in previous years include Eric Wickstrom, Ph.D., a Professor of Biochemistry and Molecular Biology at JMC and member of the KCC, and Charlene J. Williams, Ph.D., of the Department of Medicine at JMC.

Prior to his arrival at Jefferson, Dr. Schilder served as a professor in the Department of Medical Oncology and Chief of Gynecologic Medical Oncology at Fox Chase Cancer Center.

“It’s an honor to be a part of this outstanding team of highly-skilled clinicians at Jefferson,” Dr. Schilder said. “This hospital has a great reputation, particularly with their approach to individualized patient care, the latest, cutting-edge technology and research, and a much-appreciated sense of community. I’m looking forward to my time here as the director of Gynecologic Medical Oncology.”

A graduate of Rutgers University, Dr. Schilder received both his M.S. and medical degree from the University of Miami. Dr. Schilder’s postgraduate training began at Temple University Hospital with an internship and residency in Internal Medicine. In 1989, he completed a joint hematology and oncology fellowship at Temple University Hospital and Fox Chase Cancer Center.

Board-certified in internal medicine, hematology and oncology, Dr. Schilder’s research in gynecologic oncology has been published extensively in academic journals, including the Journal of Clinical Oncology and the Clinical Cancer Research. Additionally, he serves as a reviewer for academic oncology journals, including Cancer Research.

Dr. Schilder is the principal investigator for many clinical trials that study the treatment of persistent or recurrent ovarian cancer. He is also the co-principal investigator for many other clinical trials within the Gynecologic Oncology Group.

A member of several professional societies including the American Society of Clinical Oncology, American Association of Cancer Research and the International Gynecologic Cancer Society, Dr. Schilder serves on the advisory boards of several pharmaceutical companies and has presented his oncology research at national and international scientific meetings.

His research interests include evaluating new treatments for gynecologic malignancies and conducting phase I trials for new drug development. He has written more than 150 book chapters, articles, and abstracts.

“Dr. Schilder is an incredible addition to our medical oncology team,” said William Kevin Kelly, DO, Director, Division of Solid Tumor Oncology, at Thomas Jefferson University. “The hospital and university staff and our patients will greatly benefit from his wealth of knowledge, compassion and decades of medical experience in the fields of cancer and gynecology.”

Researchers at the Thomas Jefferson University Hospital and Kimmel Cancer Center at Jefferson have shown that loss of the retinoblastoma tumor suppressor gene (RB) in triple negative breast cancer patients is associated with better clinical outcomes. This is a new marker to identify the subset of these patients who may respond positively to chemotherapy.

Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same.

“This is a step in trying to better direct treatment for patients with triple negative breast cancer,” Dr. Knudsen said.

In general for cancer, loss of tumor suppressor genes is associated with poor clinical outcome. However, loss of RB in triple negative breast cancer patients appears to be a predictor of favorable clinical outcomes. This is because it changes the way tumor cells respond to therapy such that they end up becoming more sensitive to chemotherapy.

The researchers retrospectively evaluated the RB status and clinical outcome of a cohort of 220 patients diagnosed and treated at Thomas Jefferson University Hospital with chemotherapy. RB loss, they found, was associated with a longer overall survival. In contrast, patients with RB had worse survival.

“Triple negative breast cancer is the most deadly of breast cancers, with fast-growing tumors, that affects younger women,” said Dr. Witkiewicz. “This work allowed us to identify a marker that could lead to better treatment for patients. It’s about female personalized medicine.”

Edith Mitchell, M.D., Professor of Medical Oncology at Jefferson, and Adam Ertel, Ph.D., a research instructor in the Department of Cancer Biology, were also involved in the study.

The next step for the researchers is a clinical trial at Jefferson to confirm their findings. Tumors of newly-diagnosed patients with triple negative breast cancer will be tested for the RB gene before they receive chemotherapy. After treatment, the data will be evaluated to determine the efficacy of directing future patient care.

The Radiation Therapy Oncology Group (RTOG) announced that Bo Lu, M.D., Ph.D., of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, has been appointed chair of the group’s Translational Research Program (TRP) Committee’s Lung Cancer Subcommittee. The RTOG TRP Committee supports the integration of new scientific discoveries into the design of multi-center clinical trials.

Bo Lu, M.D., Ph.D., of Thomas Jefferson University Hospital and the Kimmel Cancer Center at Jefferson

Dr. Lu is professor in the Department of Radiation Oncology at Jefferson, where he also serves as director of the department’s Division of Molecular Radiation Biology. Prior to joining Jefferson in early 2011, Dr. Lu was associate professor in the Departments of Radiation Oncology and Cancer Biology at Vanderbilt University School of Medicine and director of the Department of Radiation Oncology’s translational research program. He is also a visiting professor of radiation oncology at Tianjin Medical University Cancer Hospital, in Tianjing, China.

“As a member of RTOG’s Translation Research Program Committee since 2009, it has been exciting to be part of research efforts incorporating novel cancer treatment strategies into the design of early phase, multicenter clinical trials,” says Dr. Lu. Among Dr. Lu’s basic science research interests are the development of drugs that cause tumor cells to be more sensitive to radiation therapy and that target lung cancer stem cells.

“Dr. Lu is internationally renowned for his work in translational radiation oncology, and I am enthusiastic about his leadership role with regard to guiding the RTOG’s translational research agenda in lung cancer,” says Adam Dicker, M.D., Ph.D, Professor and Chairman of Radiation O­ncology at Thomas Jefferson University and RTOG’s Translational Research Program Chair. “He has demonstrated talent for applying findings from the laboratory into clinical research,” remarks Dr. Dicker.

“The opportunity to work with RTOG colleagues to advance new treatment options and improve clinical care for lung cancer patients is very rewarding,” says Dr. Lu, “and I am pleased to assume an expanded role within a research organization that promotes the robust evaluation of new therapeutic approaches in radiation oncology.”

Dr. Lu received his Ph.D. in cell and molecular biology from Baylor School of Medicine and his doctorate in medicine from Shanghai Medical University in China. He completed his residency in radiation oncology at the University of Southern California. Dr. succeeds Quynh Le, M.D., Ph.D. from Stanford University who recently was named chair of RTOG’s Head and Neck Cancer Committee.

“An important goal at the Kimmel Cancer Center is to foster translational medicine—taking basic science research and moving it closer to clinical practice,” said Richard Pestell, M.D., Ph.D., FACP, Director of the Kimmel Cancer Center at Jefferson. “With his lab investigations focusing on just that, and now this appointment to RTOG’s lung cancer subcommittee, Dr. Lu will no doubt help us discover safer and more effective treatments for patients suffering from this disease.”

For more information about RTOG and the group’s Translational Research Program: www.rtog.org

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The Radiation Therapy Oncology Group (RTOG) is administered by the American College of Radiology (ACR), and located in the ACR Center for Clinical Research in Philadelphia, PA. RTOG is a multi-institutional international clinical cooperative group funded primarily by National Cancer Institute grants CA21661, CA32115 and CA37422. RTOG has 40 years of experience in conducting clinical trials and is comprised of over 300 major research institutions in the United States, Canada, and internationally. The group currently is currently accruing to 40 studies that involve radiation therapy alone or in conjunction with surgery and/or chemotherapeutic drugs or which investigate quality of life issues and their effects on the cancer patient.

The American College of Radiology (ACR) is a national professional organization serving more than 32,000 radiologists, radiation oncologists, interventional radiologists and medical physicists with programs focusing on the practice of radiology and the delivery of comprehensive health care services.

Researchers at the Kimmel Cancer Center at Jefferson have identified cancer cell mitochondria as the unsuspecting powerhouse and “Achilles’ heel” of tumor growth, opening up the door for new therapeutic targets in breast cancer and other tumor types.

“We and others have now shown that cancer is a ‘parasitic disease’ that steals energy from the host—your body,” Dr. Lisanti said, “but this is the first time we’ve shown in human breast tissue that cancer cell mitochondria are calling the shots and could ultimately be manipulated in our favor.”

Mitochondria are the energy-producing power-plants in normal cells. However, cancer cells have amplified this energy-producing mechanism, with at least five times as much energy-producing capacity, compared with normal cells. Simply put, mitochondria are the powerhouse of cancer cells and they fuel tumor growth and metastasis.

The research presented in the study further supports the idea that blocking this activity with a mitochondrial inhibitor—for instance, an off-patent generic drug used to treat diabetes known as Metformin—can reverse tumor growth and chemotherapy resistance. This new concept could radically change how we treat cancer patients, and stimulate new metabolic strategies for cancer prevention and therapy.

Investigating the Powerhouse

Whether cancer cells have functional mitochondria has been a hotly debated topic for the past 85 years. It was argued that cancer cells don’t use mitochondria, but instead use glycolysis exclusively; this is known as the Warburg Effect. But researchers at the Jefferson’s KCC have shown that this inefficient method of producing energy actually takes place in the surrounding host stromal cells, rather then in epithelial cancer cells. This process then provides abundant mitochondrial fuel for cancer cells. They’ve coined this the “Reverse Warburg Effect,” the opposite or reverse of the existing paradigm.

Researchers found that human breast cancer epithelial cells showed amplified levels of mitochondrial activity. In contrast, adjacent stromal tissues showed little or no mitochondrial oxidative capacity, consistent with the new paradigm. These findings were further validated using a computer-based informatics approach with gene profiles from over 2,000 human breast cancer samples.

It is now clear that cancer cell mitochondria play a key role in “parasitic” energy transfer between normal fibroblasts and cancer cells, fueling tumor growth and metastasis.

“We have presented new evidence that cancer cell mitochondria are at the heart of tumor cell growth and metastasis,” Dr. Lisanti said. “Metabolically, the drug Metformin prevents cancer cells from using their mitochondria, induces glycolysis and lactate production, and shifts cancer cells toward the conventional ‘Warburg Effect’. This effectively starves the cancer cells to death”.

Personalized Treatment

Although COX mitochondrial activity staining had never been applied to cancer tissues, it could now be used routinely to distinguish cancer cells from normal cells, and to establish negative margins during cancer surgery. And this is a very cost-effective test, since it has been used routinely for muscle-tissue for over 50 years, but not for cancer diagnosis.

What’s more, it appears that upregulation of mitochondrial activity is a common feature of human breast cancer cells, and is associated with both estrogen receptor positive (ER+) and negative (ER-) disease. Outcome analysis indicated that this mitochondrial gene signature is also associated with an increased risk of tumor cell metastasis, particularly in ER-negative (ER-) patients.

“Mitochondria are the ‘Achilles’ heel’ of tumor cells,” Dr. Lisanti said. “And we believe that targeting mitochondrial metabolism has broad implications for both cancer diagnostics and therapeutics, and could be exploited in the pursuit of personalized cancer medicine.”

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